A novel deep proteomic approach in human skeletal muscle unveils distinct molecular signatures affected by aging and resistance training.

The skeletal muscle proteome alterations to aging and resistance training have been reported in prior studies. However, conventional proteomics in skeletal muscle typically yields wide protein abundance ranges that mask the detection of lowly expressed proteins. Thus, we adopted a novel deep proteomics approach whereby myofibril (MyoF) and non-MyoF fractions were separately subjected to protein corona nanoparticle complex formation prior to digestion and Liquid Chromatography Mass Spectrometry (LC-MS). Specifically, we investigated MyoF and non-MyoF proteomic profiles of the vastus lateralis muscle of younger (Y, 22±2 years old; n=5) and middle-aged participants (MA, 56±8 years old; n=6). Additionally, MA muscle was analyzed following eight weeks of resistance training (RT, 2d/week). Across all participants, the number of non-MyoF proteins detected averaged to be 5,645±266 (range: 4,888-5,987) and the number of MyoF proteins detected averaged to be 2,611±326 (range: 1,944-3,101). Differences in the non-MyoF (8.4%) and MyoF (2.5%) proteomes were evident between age cohorts, and most differentially expressed non-MyoF proteins (447/543) were more enriched in MA versus Y. Biological processes in the non-MyoF fraction were predicted to be operative in MA versus Y including increased cellular stress, mRNA splicing, translation elongation, and ubiquitin-mediated proteolysis. RT in MA participants only altered ~0.3% of MyoF and ~1.0% of non-MyoF proteomes. In summary, aging and RT predominantly affect non-contractile proteins in skeletal muscle. Additionally, marginal proteome adaptations with RT suggest more rigorous training may stimulate more robust effects or that RT, regardless of age, subtly alters basal state skeletal muscle protein abundances.

The effects of resistance training on denervated myofibers, senescent cells, and associated protein markers in middle-aged adults.

Denervated myofibers and senescent cells are hallmarks of skeletal muscle aging. However, sparse research has examined how resistance training affects these outcomes. We investigated the effects of unilateral leg extensor resistance training (2 days/week for 8 weeks) on denervated myofibers, senescent cells, and associated protein markers in apparently healthy middle-aged participants (MA, 55 ± 8 years old, 17 females, 9 males). We obtained dual-leg vastus lateralis (VL) muscle cross-sectional area (mCSA), VL biopsies, and strength assessments before and after training. Fiber cross-sectional area (fCSA), satellite cells (Pax7+), denervated myofibers (NCAM+), senescent cells (p16+ or p21+), proteins associated with denervation and senescence, and senescence-associated secretory phenotype (SASP) proteins were analyzed from biopsy specimens. Leg extensor peak torque increased after training (p < .001), while VL mCSA trended upward (interaction p = .082). No significant changes were observed for Type I/II fCSAs, NCAM+ myofibers, or senescent (p16+ or p21+) cells, albeit satellite cells increased after training (p = .037). While >90% satellite cells were not p16+ or p21+, most p16+ and p21+ cells were Pax7+ (>90% on average). Training altered 13 out of 46 proteins related to muscle-nerve communication (all upregulated, p < .05) and 10 out of 19 proteins related to cellular senescence (9 upregulated, p < .05). Only 1 out of 17 SASP protein increased with training (IGFBP-3, p = .031). In conclusion, resistance training upregulates proteins associated with muscle-nerve communication in MA participants but does not alter NCAM+ myofibers. Moreover, while training increased senescence-related proteins, this coincided with an increase in satellite cells but not alterations in senescent cell content or SASP proteins. These latter findings suggest shorter term resistance training is an unlikely inducer of cellular senescence in apparently healthy middle-aged participants. However, similar study designs are needed in older and diseased populations before definitive conclusions can be drawn.

Acute Effects of Naturally Occurring Guayusa Tea and Nordic Lion's Mane Extracts on Cognitive Performance.

The aim of this study was to assess the effects of guayusa extract and Nordic Lion's Mane (LM) on cognition. Using a randomized, double-blind, placebo-controlled, crossover design, we examined the effects of a single dose of 650 mg guayusa extract (AMT: AmaTea® Max) vs. 1 g Nordic-grown Lion's Mane (LM) vs. placebo (PL). Participants attended three testing visits consisting of neuropsychological tests (Go/No-go, N-Back, and Serial 7 s tasks) assessing performance, subjective assessments of cognitive perception, and vital signs. Each assessment was measured at baseline (pre-ingestion) and 1 and 2 h post ingestion. AMT significantly (p ≤ 0.05) improved the number of attempts during Serial 7s, total score, number of correct responses, total number of responses, and reaction time during N-Back and improved Go stimulus reaction time, but it reduced the percentage of correct responses in the No-go stimulus response during Go/No-go. LM significantly (p ≤ 0.05) improved the number of attempts during Serial 7s and reaction time during N-Back and improved Go stimulus reaction time in Go/No-go. AMT improved mental clarity, focus, concentration, mood, and productivity at 1 and 2 h (p < 0.05); the ability to tolerate stress at 1 h; and had greater ratings than LM and PL for mental clarity, focus, concentration, and productivity. PL improved focus and concentration at 1 h from baseline (p ≤ 0.05). AMT and LM improved subjective ratings of "happiness compared to peers" and "getting the most out of everything" (p < 0.05); however, this occurred earlier in LM (i.e., 1 h post ingestion). AMT uniquely elevated blood pressure from baseline. AMT significantly improved cognitive performance and self-perceived cognitive indices of affect over a 2 h period and perceptions of happiness 2 h post ingestion. In comparison, LM helped improve working memory, complex attention, and reaction time 2 h post ingestion and perceptions of happiness over a 2 h period.

International society of sports nutrition position stand: coffee and sports performance.

Based on review and critical analysis of the literature regarding the contents and physiological effects of coffee related to physical and cognitive performance conducted by experts in the field and selected members of the International Society of Sports Nutrition (ISSN), the following conclusions represent the official Position of the Society:(1) Coffee is a complex matrix of hundreds of compounds. These are consumed with broad variability based upon serving size, bean type (e.g. common Arabica vs. Robusta), and brew method (water temperature, roasting method, grind size, time, and equipment).(2) Coffee's constituents, including but not limited to caffeine, have neuromuscular, antioxidant, endocrine, cognitive, and metabolic (e.g. glucose disposal and vasodilation) effects that impact exercise performance and recovery.(3) Coffee's physiologic effects are influenced by dose, timing, habituation to a small degree (to coffee or caffeine), nutrigenetics, and potentially by gut microbiota differences, sex, and training status.(4) Coffee and/or its components improve performance across a temporal range of activities from reaction time, through brief power exercises, and into the aerobic time frame in most but not all studies. These broad and varied effects have been demonstrated in men (mostly) and in women, with effects that can differ from caffeine ingestion, per se. More research is needed.(5) Optimal dosing and timing are approximately two to four cups (approximately 473-946 ml or 16-32 oz.) of typical hot-brewed or reconstituted instant coffee (depending on individual sensitivity and body size), providing a caffeine equivalent of 3-6 mg/kg (among other components such as chlorogenic acids at approximately 100-400 mg per cup) 60 min prior to exercise.(6) Coffee has a history of controversy regarding side effects but is generally considered safe and beneficial for healthy, exercising individuals in the dose range above.(7) Coffee can serve as a vehicle for other dietary supplements, and it can interact with nutrients in other foods.(8) A dearth of literature exists examining coffee-specific ergogenic and recovery effects, as well as variability in the operational definition of "coffee," making conclusions more challenging than when examining caffeine in its many other forms of delivery (capsules, energy drinks, "pre-workout" powders, gum, etc.).

A novel deep proteomic approach in human skeletal muscle unveils distinct molecular signatures affected by aging and resistance training.

We examined the myofibrillar (MyoF) and non-myofibrillar (non-MyoF) proteomic profiles of the vastus lateralis (VL) muscle of younger (Y, 22±2 years old; n=5) and middle-aged participants (MA, 56±8 years old; n=6), and MA following eight weeks of knee extensor resistance training (RT, 2d/week). Shotgun/bottom-up proteomics in skeletal muscle typically yields wide protein abundance ranges that mask lowly expressed proteins. Thus, we adopted a novel approach whereby the MyoF and non-MyoF fractions were separately subjected to protein corona nanoparticle complex formation prior to digestion and Liquid Chromatography Mass Spectrometry (LC-MS) analysis. A total of 10,866 proteins (4,421 MyoF and 6,445 non-MyoF) were identified. Across all participants, the number of non-MyoF proteins detected averaged to be 5,645±266 (range: 4,888-5,987) and the number of MyoF proteins detected averaged to be 2,611±326 (range: 1,944-3,101). Differences in the non-MyoF (8.4%) and MyoF (2.5%) proteome were evident between age cohorts. Further, most of these age-related non-MyoF proteins (447/543) were more enriched in MA versus Y. Several biological processes in the non-MyoF fraction were predicted to be operative in MA versus Y including (but not limited to) increased cellular stress, mRNA splicing, translation elongation, and ubiquitin-mediated proteolysis. Non-MyoF proteins associated with splicing and proteostasis were further interrogated, and in agreement with bioinformatics, alternative protein variants, spliceosome-associated proteins (snRNPs), and proteolysis-related targets were more abundant in MA versus Y. RT in MA non-significantly increased VL muscle cross-sectional area (+6.5%, p=0.066) and significantly increased knee extensor strength (+8.7%, p=0.048). However, RT modestly altered the MyoF (~0.3%, 11 upregulated and two downregulated proteins) and non-MyoF proteomes (~1.0%, 56 upregulated and eight downregulated proteins, p<0.01). Further, RT did not affect predicted biological processes in either fraction. Although participant numbers were limited, these preliminary results using a novel deep proteomic approach in skeletal muscle suggest that aging and RT predominantly affects protein abundances in the non-contractile protein pool. However, the marginal proteome adaptations occurring with RT suggest either: a) this may be an aging-associated phenomenon, b) more rigorous RT may stimulate more robust effects, or c) RT, regardless of age, subtly affects skeletal muscle protein abundances in the basal state.

Different Resistance Exercise Loading Paradigms Similarly Affect Skeletal Muscle Gene Expression Patterns of Myostatin-Related Targets and mTORC1 Signaling Markers.

Although transcriptome profiling has been used in several resistance training studies, the associated analytical approaches seldom provide in-depth information on individual genes linked to skeletal muscle hypertrophy. Therefore, a secondary analysis was performed herein on a muscle transcriptomic dataset we previously published involving trained college-aged men (n = 11) performing two resistance exercise bouts in a randomized and crossover fashion. The lower-load bout (30 Fail) consisted of 8 sets of lower body exercises to volitional fatigue using 30% one-repetition maximum (1 RM) loads, whereas the higher-load bout (80 Fail) consisted of the same exercises using 80% 1 RM loads. Vastus lateralis muscle biopsies were collected prior to (PRE), 3 h, and 6 h after each exercise bout, and 58 genes associated with skeletal muscle hypertrophy were manually interrogated from our prior microarray data. Select targets were further interrogated for associated protein expression and phosphorylation induced-signaling events. Although none of the 58 gene targets demonstrated significant bout x time interactions, ~57% (32 genes) showed a significant main effect of time from PRE to 3 h (15↑ and 17↓, p < 0.01), and ~26% (17 genes) showed a significant main effect of time from PRE to 6 h (8↑ and 9↓, p < 0.01). Notably, genes associated with the myostatin (9 genes) and mammalian target of rapamycin complex 1 (mTORC1) (9 genes) signaling pathways were most represented. Compared to mTORC1 signaling mRNAs, more MSTN signaling-related mRNAs (7 of 9) were altered post-exercise, regardless of the bout, and RHEB was the only mTORC1-associated mRNA that was upregulated following exercise. Phosphorylated (phospho-) p70S6K (Thr389) (p = 0.001; PRE to 3 h) and follistatin protein levels (p = 0.021; PRE to 6 h) increased post-exercise, regardless of the bout, whereas phospho-AKT (Thr389), phospho-mTOR (Ser2448), and myostatin protein levels remained unaltered. These data continue to suggest that performing resistance exercise to volitional fatigue, regardless of load selection, elicits similar transient mRNA and signaling responses in skeletal muscle. Moreover, these data provide further evidence that the transcriptional regulation of myostatin signaling is an involved mechanism in response to resistance exercise.

Skeletal Muscle DNA Methylation and mRNA Responses to a Bout of Higher versus Lower Load Resistance Exercise in Previously Trained Men.

We sought to determine the skeletal muscle genome-wide DNA methylation and mRNA responses to one bout of lower load (LL) versus higher load (HL) resistance exercise. Trained college-aged males (n = 11, 23 ± 4 years old, 4 ± 3 years self-reported training) performed LL or HL bouts to failure separated by one week. The HL bout (i.e., 80 Fail) consisted of four sets of back squats and four sets of leg extensions to failure using 80% of participants estimated one-repetition maximum (i.e., est. 1-RM). The LL bout (i.e., 30 Fail) implemented the same paradigm with 30% of est. 1-RM. Vastus lateralis muscle biopsies were collected before, 3 h, and 6 h after each bout. Muscle DNA and RNA were batch-isolated and analyzed using the 850k Illumina MethylationEPIC array and Clariom S mRNA microarray, respectively. Performed repetitions were significantly greater during the 30 Fail versus 80 Fail (p < 0.001), although total training volume (sets × reps × load) was not significantly different between bouts (p = 0.571). Regardless of bout, more CpG site methylation changes were observed at 3 h versus 6 h post exercise (239,951 versus 12,419, respectively; p < 0.01), and nuclear global ten-eleven translocation (TET) activity, but not global DNA methyltransferase activity, increased 3 h and 6 h following exercise regardless of bout. The percentage of genes significantly altered at the mRNA level that demonstrated opposite DNA methylation patterns was greater 3 h versus 6 h following exercise (~75% versus ~15%, respectively). Moreover, high percentages of genes that were up- or downregulated 6 h following exercise also demonstrated significantly inversed DNA methylation patterns across one or more CpG sites 3 h following exercise (65% and 82%, respectively). While 30 Fail decreased DNA methylation across various promoter regions versus 80 Fail, transcriptome-wide mRNA and bioinformatics indicated that gene expression signatures were largely similar between bouts. Bioinformatics overlay of DNA methylation and mRNA expression data indicated that genes related to "Focal adhesion," "MAPK signaling," and "PI3K-Akt signaling" were significantly affected at the 3 h and 6 h time points, and again this was regardless of bout. In conclusion, extensive molecular profiling suggests that post-exercise alterations in the skeletal muscle DNA methylome and mRNA transcriptome elicited by LL and HL training bouts to failure are largely similar, and this could be related to equal volumes performed between bouts.

International society of sports nutrition position stand: tactical athlete nutrition.

This position stand aims to provide an evidence-based summary of the energy and nutritional demands of tactical athletes to promote optimal health and performance while keeping in mind the unique challenges faced due to work schedules, job demands, and austere environments. After a critical analysis of the literature, the following nutritional guidelines represent the position of the International Society of Sports Nutrition (ISSN). General Recommendations: Nutritional considerations should include the provision and timing of adequate calories, macronutrients, and fluid to meet daily needs as well as strategic nutritional supplementation to improve physical, cognitive, and occupational performance outcomes; reduce risk of injury, obesity, and cardiometabolic disease; reduce the potential for a fatal mistake; and promote occupational readiness. Military Recommendations: Energy demands should be met by utilizing the Military Dietary Reference Intakes (MDRIs) established and codified in Army Regulation 40-25. Although research is somewhat limited, military personnel may also benefit from caffeine, creatine monohydrate, essential amino acids, protein, omega-3-fatty acids, beta-alanine, and L-tyrosine supplementation, especially during high-stress conditions. First Responder Recommendations: Specific energy needs are unknown and may vary depending on occupation-specific tasks. It is likely the general caloric intake and macronutrient guidelines for recreational athletes or the Acceptable Macronutrient Distribution Ranges for the general healthy adult population may benefit first responders. Strategies such as implementing wellness policies, setting up supportive food environments, encouraging healthier food systems, and using community resources to offer evidence-based nutrition classes are inexpensive and potentially meaningful ways to improve physical activity and diet habits. The following provides a more detailed overview of the literature and recommendations for these populations.

International Society of Sports Nutrition position stand: sodium bicarbonate and exercise performance.

Based on a comprehensive review and critical analysis of the literature regarding the effects of sodium bicarbonate supplementation on exercise performance, conducted by experts in the field and selected members of the International Society of Sports Nutrition (ISSN), the following conclusions represent the official Position of the Society: 1. Supplementation with sodium bicarbonate (doses from 0.2 to 0.5 g/kg) improves performance in muscular endurance activities, various combat sports, including boxing, judo, karate, taekwondo, and wrestling, and in high-intensity cycling, running, swimming, and rowing. The ergogenic effects of sodium bicarbonate are mostly established for exercise tasks of high-intensity that last between 30 s and 12 min. 2. Sodium bicarbonate improves performance in single- and multiple-bout exercise. 3. Sodium bicarbonate improves exercise performance in both men and women. 4. For single-dose supplementation protocols, 0.2 g/kg of sodium bicarbonate seems to be the minimum dose required to experience improvements in exercise performance. The optimal dose of sodium bicarbonate dose for ergogenic effects seems to be 0.3 g/kg. Higher doses (e.g., 0.4 or 0.5 g/kg) may not be required in single-dose supplementation protocols, because they do not provide additional benefits (compared with 0.3 g/kg) and are associated with a higher incidence and severity of adverse side-effects. 5. For single-dose supplementation protocols, the recommended timing of sodium bicarbonate ingestion is between 60 and 180 min before exercise or competition. 6. Multiple-day protocols of sodium bicarbonate supplementation can be effective in improving exercise performance. The duration of these protocols is generally between 3 and 7 days before the exercise test, and a total sodium bicarbonate dose of 0.4 or 0.5 g/kg per day produces ergogenic effects. The total daily dose is commonly divided into smaller doses, ingested at multiple points throughout the day (e.g., 0.1 to 0.2 g/kg of sodium bicarbonate consumed at breakfast, lunch, and dinner). The benefit of multiple-day protocols is that they could help reduce the risk of sodium bicarbonate-induced side-effects on the day of competition. 7. Long-term use of sodium bicarbonate (e.g., before every exercise training session) may enhance training adaptations, such as increased time to fatigue and power output. 8. The most common side-effects of sodium bicarbonate supplementation are bloating, nausea, vomiting, and abdominal pain. The incidence and severity of side-effects vary between and within individuals, but it is generally low. Nonetheless, these side-effects following sodium bicarbonate supplementation may negatively impact exercise performance. Ingesting sodium bicarbonate (i) in smaller doses (e.g., 0.2 g/kg or 0.3 g/kg), (ii) around 180 min before exercise or adjusting the timing according to individual responses to side-effects, (iii) alongside a high-carbohydrate meal, and (iv) in enteric-coated capsules are possible strategies to minimize the likelihood and severity of these side-effects. 9. Combining sodium bicarbonate with creatine or beta-alanine may produce additive effects on exercise performance. It is unclear whether combining sodium bicarbonate with caffeine or nitrates produces additive benefits. 10. Sodium bicarbonate improves exercise performance primarily due to a range of its physiological effects. Still, a portion of the ergogenic effect of sodium bicarbonate seems to be placebo-driven.

Common questions and misconceptions about creatine supplementation: what does the scientific evidence really show?

Supplementing with creatine is very popular amongst athletes and exercising individuals for improving muscle mass, performance and recovery. Accumulating evidence also suggests that creatine supplementation produces a variety of beneficial effects in older and patient populations. Furthermore, evidence-based research shows that creatine supplementation is relatively well tolerated, especially at recommended dosages (i.e. 3-5 g/day or 0.1 g/kg of body mass/day). Although there are over 500 peer-refereed publications involving creatine supplementation, it is somewhat surprising that questions regarding the efficacy and safety of creatine still remain. These include, but are not limited to: 1. Does creatine lead to water retention? 2. Is creatine an anabolic steroid? 3. Does creatine cause kidney damage/renal dysfunction? 4. Does creatine cause hair loss / baldness? 5. Does creatine lead to dehydration and muscle cramping? 6. Is creatine harmful for children and adolescents? 7. Does creatine increase fat mass? 8. Is a creatine 'loading-phase' required? 9. Is creatine beneficial for older adults? 10. Is creatine only useful for resistance / power type activities? 11. Is creatine only effective for males? 12. Are other forms of creatine similar or superior to monohydrate and is creatine stable in solutions/beverages? To answer these questions, an internationally renowned team of research experts was formed to perform an evidence-based scientific evaluation of the literature regarding creatine supplementation.

Resistance training increases muscle NAD+ and NADH concentrations as well as NAMPT protein levels and global sirtuin activity in middle-aged, overweight, untrained individuals.

We examined if resistance training affected muscle NAD+ and NADH concentrations as well as nicotinamide phosphoribosyltransferase (NAMPT) protein levels and sirtuin (SIRT) activity markers in middle-aged, untrained (MA) individuals. MA participants (59±4 years old; n=16) completed 10 weeks of full-body resistance training (2 d/wk). Body composition, knee extensor strength, and vastus lateralis muscle biopsies were obtained prior to training (Pre) and 72 hours following the last training bout (Post). Data from trained college-aged men (22±3 years old, training age: 6±2 years old; n=15) were also obtained for comparative purposes. Muscle NAD+ (+127%, p<0.001), NADH (+99%, p=0.002), global SIRT activity (+13%, p=0.036), and NAMPT protein (+15%, p=0.014) increased from Pre to Post in MA participants. Additionally, Pre muscle NAD+ and NADH in MA participants were lower than college-aged participants (p<0.05), whereas Post values were similar between cohorts (p>0.10). Interestingly, muscle citrate synthase activity levels (i.e., mitochondrial density) increased in MA participants from Pre to Post (+183%, p<0.001), and this increase was significantly associated with increases in muscle NAD+ (r2=0.592, p=0.001). In summary, muscle NAD+, NADH, and global SIRT activity are positively affected by resistance training in middle-aged, untrained individuals. Whether these adaptations facilitated mitochondrial biogenesis remains to be determined.

Effects of Hemp Extract on Markers of Wellness, Stress Resilience, Recovery and Clinical Biomarkers of Safety in Overweight, But Otherwise Healthy Subjects.

We determined the effects of a commercially available, GRAS (Generally Recognized As Safe) by independent conclusion, CBD-containing hemp oil extract on stress resilience, perceived recovery, mood, affect, body composition, and clinical safety markers in healthy human subjects.Methods: Using a randomized, placebo-controlled, double-blind design, 65 overweight, but otherwise healthy men and women (35.2 ± 11.4 years, 28.5 ± 3.3 kg/m2) ingested either Hemp Oil Extract [Hemp, 60 mg/d PlusCBDTM Extra Strength Hemp Extract Oil (15 mg hemp-derived CBD)] or a placebo (PLA) every day for six weeks while continuing to follow their normal diet and physical activity patterns. Outcome variables included changes in stress resilience, a 14-item panel of various psychometric parameters, heart-rate variability, plasma chromogranin A, body composition, and general markers of health. Data were analyzed using mixed factorial ANOVA, t-tests with 95% confidence intervals, and effect sizes (ES).Results: HDL cholesterol significantly improved in the Hemp group (p = 0.004; ES = 0.75). No other statistically significant group x time interaction effects were observed. Statistical tendencies for between-group differences were found for 'I Get Pleasure From Life' (p = 0.06, ES = 0.48) and 'Ability to Cope with Stress' (p = 0.07, ES = 0.46). Sleep quality (Hemp, p = 0.005, ES = 0.54) and sleep quantity (Hemp, p = 0.01, ES = 0.58) exhibited significant within-group changes. All values for hepato-renal function, cardiovascular health, fasting blood lipids, and whole blood cell counts remained within normal clinical limits with no between-group differences over time being identified.Conclusions: Hemp supplementation improved HDL cholesterol, tended to support psychometric measures of perceived sleep, stress response, and perceived life pleasure and was well tolerated with no clinically relevant safety concerns. Registered at clinicaltrials.gov: NCT04294706.

Proprietary Milk Protein Concentrate Reduces Joint Discomfort While Improving Exercise Performance in Non-Osteoarthritic Individuals.

Milk and dairy products are known to contain various bioactives with potential anti-inflammatory and immune modulating effects. Previous research has indicated that milk produced from hyperimmunized cows provided meaningful health benefits to individuals suffering from varying degrees of osteoarthritis and rheumatoid arthritis. PURPOSE: To examine the impact of MicroLactin®, a proprietary milk protein concentrate, on joint discomfort and physical function, exercise performance, quality of life and various measures of affect. METHODS: Non-osteoarthritic men (42.5 ± 8.9 years, 176.7 ± 6.7 cm, 89.9 ± 11.5 kg, 28.8 ± 3.5 kg/m², n = 30) and women (46.4 ± 9.6 years, 163.1 ± 8.2 cm, 72.2 ± 13.1 kg, 27.2 ± 5.3 kg/m², n = 28) with mild to moderate knee pain during physical activity were randomized in a double-blind, placebo-controlled fashion to consume daily either a placebo (PLA) or MicroLactin® (ML) for a period of 8 weeks. Participants completed a functional capacity test pre and post-supplementation and completed visual analog scales (VAS), a 6-min walking test, WOMAC and profile of mood states (POMS) to assess changes in joint health, discomfort, physical function, exercise performance and affect. Mixed factorial ANOVA was used for all statistical analysis and significance was set a priori at p ≤ 0.05. RESULTS: Distance covered in the 6-min walking significantly improved 9% in ML versus 2% in PLA (mean difference: 110 ± 43 m, p = 0.012) in addition to 11 WOMAC components and 5 VAS reflective of ML improving joint health, discomfort and joint stability (all p < 0.05 vs. PLA). Additionally, ML also improved overall perceptions of neck and back health compared to PLA. Serum and whole blood indicators of clinical safety remained within normal ranges throughout the study. CONCLUSIONS: In comparison to placebo, daily doses of MicroLactin® yielded improvements in several components of the WOMAC, multiple visual analog scales indicative of joint health and stability, discomfort and pain, as well as significant improvements in distance covered during a 6-min walking test. Supplementation was well tolerated with no significant changes in whole-blood or serum markers of clinical safety.

Effects of an Aqueous Extract of Withania somnifera on Strength Training Adaptations and Recovery: The STAR Trial.

Withania somnifera (Ashwagandha) is an Ayurvedic herb categorized as having "rasayana" (rejuvenator), longevity, and revitalizing properties. Sensoril® is a standardized aqueous extract of the roots and leaves of Withania somnifera. Purpose: To examine the impact of Sensoril® supplementation on strength training adaptations. Methods: Recreationally active men (26.5 ± 6.4 years, 181 ± 6.8 cm, 86.9 ± 12.5 kg, 24.5 ± 6.6% fat) were randomized in a double-blind fashion to placebo (PLA, n = 19) or 500 mg/d Sensoril® (S500, n = 19). Body composition (DEXA), muscular strength, power, and endurance, 7.5 km cycling time trial, and clinical blood chemistries were measured at baseline and after 12 weeks of supplementation and training. Subjects were required to maintain their normal dietary habits and to follow a specific, progressive overload resistance-training program (4-day/week, upper body/lower body split). 2 × 2 mixed factorial ANOVA was used for analysis and statistical significance was set a priori at p ≤ 0.05. Results: Gains in 1-RM squat (S500: +19.1 ± 13.0 kg vs. PLA +10.0 ± 6.2 kg, p = 0.009) and bench press (S500: +12.8 ± 8.2 kg vs. PLA: +8.0 ± 6.0 kg, p = 0.048) were significantly greater in S500. Changes in DEXA-derived android/gynoid ratio (S500: +0.0 ± 0.14 vs. PLA: +0.09 ± 0.1, p = 0.03) also favored S500. No other between-group differences were found for body composition, visual analog scales for recovery and affect, or systemic hemodynamics, however, only the S500 group experienced statistically significant improvements in average squat power, peak bench press power, 7.5 km time trial performance, and perceived recovery scores. Clinical chemistry analysis indicated a slight polycythemia effect in PLA, with no other statistical or clinically relevant changes being noted. Conclusions: A 500 mg dose of an aqueous extract of Ashwagandha improves upper and lower-body strength, supports a favorable distribution of body mass, and was well tolerated clinically in recreationally active men over a 12-week resistance training and supplementation period.

The Combined Effects of Exercise, Diet, and a Multi-Ingredient Dietary Supplement on Body Composition and Adipokine Changes in Overweight Adults.

BACKGROUND: Very few weight and fat loss supplements undergo finished-product research to examine efficacy. The purpose of this study was to determine the effects of an 8-week diet and exercise program on body composition, hip and waist girth, and adipokines and evaluate whether a dietary supplement containing raspberry ketone, capsaicin, caffeine, garlic, and Citrus aurantium enhanced outcomes. METHODS: Overweight men and women completed this randomized, placebo-controlled, double-blind study. Participants consumed 4 capsules/d of supplement (EXP; n = 18) or placebo (PLA; n = 18). Participants underwent 8 weeks of daily supplementation, calorie restriction (500 kcal < RMR [resting metabolic rate] × 1.2), and supervised progressive exercise training 3 times a week. Body composition, girth, and adipokines were assessed at baseline and postintervention (T1 and T2). RESULTS: Significant decreases in weight (-2.6 ± 0.57 kg, p < 0.001), fat mass (-1.8 ± 0.20 kg; p < 0.001), and percentage body fat (-3.7% ± 0.29%, p < 0.001) and a significant increase in lean body mass (LBM; 1.5 ± 0.26 kg; p < 0.001) were seen from T1 to T2 in both groups. For men, only those in the EXP group increased LBM from T1 to T2 (1.3 ± 0.38 kg; p < 0.05). Hip girth was also reduced, with the women in the EXP group (-10.7 ± 2.15 cm, p < 0.001) having a greater reduction. There was a time by group interaction, with significant decreases in leptin (p < 0.001) and significant increases in adiponectin (p < 0.05) in the EXP group. CONCLUSIONS: Significant improvements in adipokines and leptin support the utility of exercise, diet, and fat loss for impacting inflammatory biomarkers. The improvement in adiponectin with EXP may suggest a unique health mechanism.

International society of sports nutrition position stand: nutrient timing.

The International Society of Sports Nutrition (ISSN) provides an objective and critical review regarding the timing of macronutrients in reference to healthy, exercising adults and in particular highly trained individuals on exercise performance and body composition. The following points summarize the position of the ISSN:Nutrient timing incorporates the use of methodical planning and eating of whole foods, fortified foods and dietary supplements. The timing of energy intake and the ratio of certain ingested macronutrients may enhance recovery and tissue repair, augment muscle protein synthesis (MPS), and improve mood states following high-volume or intense exercise.Endogenous glycogen stores are maximized by following a high-carbohydrate diet (8-12 g of carbohydrate/kg/day [g/kg/day]); moreover, these stores are depleted most by high volume exercise.If rapid restoration of glycogen is required (< 4 h of recovery time) then the following strategies should be considered:aggressive carbohydrate refeeding (1.2 g/kg/h) with a preference towards carbohydrate sources that have a high (> 70) glycemic indexthe addition of caffeine (3-8 mg/kg)combining carbohydrates (0.8 g/kg/h) with protein (0.2-0.4 g/kg/h) Extended (> 60 min) bouts of high intensity (> 70% VO2max) exercise challenge fuel supply and fluid regulation, thus carbohydrate should be consumed at a rate of ~30-60 g of carbohydrate/h in a 6-8% carbohydrate-electrolyte solution (6-12 fluid ounces) every 10-15 min throughout the entire exercise bout, particularly in those exercise bouts that span beyond 70 min. When carbohydrate delivery is inadequate, adding protein may help increase performance, ameliorate muscle damage, promote euglycemia and facilitate glycogen re-synthesis.Carbohydrate ingestion throughout resistance exercise (e.g., 3-6 sets of 8-12 repetition maximum [RM] using multiple exercises targeting all major muscle groups) has been shown to promote euglycemia and higher glycogen stores. Consuming carbohydrate solely or in combination with protein during resistance exercise increases muscle glycogen stores, ameliorates muscle damage, and facilitates greater acute and chronic training adaptations.Meeting the total daily intake of protein, preferably with evenly spaced protein feedings (approximately every 3 h during the day), should be viewed as a primary area of emphasis for exercising individuals.Ingestion of essential amino acids (EAA; approximately 10 g)either in free form or as part of a protein bolus of approximately 20-40 g has been shown to maximally stimulate muscle protein synthesis (MPS).Pre- and/or post-exercise nutritional interventions (carbohydrate + protein or protein alone) may operate as an effective strategy to support increases in strength and improvements in body composition. However, the size and timing of a pre-exercise meal may impact the extent to which post-exercise protein feeding is required.Post-exercise ingestion (immediately to 2-h post) of high-quality protein sources stimulates robust increases in MPS.In non-exercising scenarios, changing the frequency of meals has shown limited impact on weight loss and body composition, with stronger evidence to indicate meal frequency can favorably improve appetite and satiety. More research is needed to determine the influence of combining an exercise program with altered meal frequencies on weight loss and body composition with preliminary research indicating a potential benefit.Ingesting a 20-40 g protein dose (0.25-0.40 g/kg body mass/dose) of a high-quality source every three to 4 h appears to most favorably affect MPS rates when compared to other dietary patterns and is associated with improved body composition and performance outcomes.Consuming casein protein (~ 30-40 g) prior to sleep can acutely increase MPS and metabolic rate throughout the night without influencing lipolysis.

International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine.

Creatine is one of the most popular nutritional ergogenic aids for athletes. Studies have consistently shown that creatine supplementation increases intramuscular creatine concentrations which may help explain the observed improvements in high intensity exercise performance leading to greater training adaptations. In addition to athletic and exercise improvement, research has shown that creatine supplementation may enhance post-exercise recovery, injury prevention, thermoregulation, rehabilitation, and concussion and/or spinal cord neuroprotection. Additionally, a number of clinical applications of creatine supplementation have been studied involving neurodegenerative diseases (e.g., muscular dystrophy, Parkinson's, Huntington's disease), diabetes, osteoarthritis, fibromyalgia, aging, brain and heart ischemia, adolescent depression, and pregnancy. These studies provide a large body of evidence that creatine can not only improve exercise performance, but can play a role in preventing and/or reducing the severity of injury, enhancing rehabilitation from injuries, and helping athletes tolerate heavy training loads. Additionally, researchers have identified a number of potentially beneficial clinical uses of creatine supplementation. These studies show that short and long-term supplementation (up to 30 g/day for 5 years) is safe and well-tolerated in healthy individuals and in a number of patient populations ranging from infants to the elderly. Moreover, significant health benefits may be provided by ensuring habitual low dietary creatine ingestion (e.g., 3 g/day) throughout the lifespan. The purpose of this review is to provide an update to the current literature regarding the role and safety of creatine supplementation in exercise, sport, and medicine and to update the position stand of International Society of Sports Nutrition (ISSN).

International Society of Sports Nutrition Position Stand: protein and exercise.

The International Society of Sports Nutrition (ISSN) provides an objective and critical review related to the intake of protein for healthy, exercising individuals. Based on the current available literature, the position of the Society is as follows:An acute exercise stimulus, particularly resistance exercise, and protein ingestion both stimulate muscle protein synthesis (MPS) and are synergistic when protein consumption occurs before or after resistance exercise.For building muscle mass and for maintaining muscle mass through a positive muscle protein balance, an overall daily protein intake in the range of 1.4-2.0 g protein/kg body weight/day (g/kg/d) is sufficient for most exercising individuals, a value that falls in line within the Acceptable Macronutrient Distribution Range published by the Institute of Medicine for protein.Higher protein intakes (2.3-3.1 g/kg/d) may be needed to maximize the retention of lean body mass in resistance-trained subjects during hypocaloric periods.There is novel evidence that suggests higher protein intakes (>3.0 g/kg/d) may have positive effects on body composition in resistance-trained individuals (i.e., promote loss of fat mass).Recommendations regarding the optimal protein intake per serving for athletes to maximize MPS are mixed and are dependent upon age and recent resistance exercise stimuli. General recommendations are 0.25 g of a high-quality protein per kg of body weight, or an absolute dose of 20-40 g.Acute protein doses should strive to contain 700-3000 mg of leucine and/or a higher relative leucine content, in addition to a balanced array of the essential amino acids (EAAs).These protein doses should ideally be evenly distributed, every 3-4 h, across the day.The optimal time period during which to ingest protein is likely a matter of individual tolerance, since benefits are derived from pre- or post-workout ingestion; however, the anabolic effect of exercise is long-lasting (at least 24 h), but likely diminishes with increasing time post-exercise.While it is possible for physically active individuals to obtain their daily protein requirements through the consumption of whole foods, supplementation is a practical way of ensuring intake of adequate protein quality and quantity, while minimizing caloric intake, particularly for athletes who typically complete high volumes of training. Rapidly digested proteins that contain high proportions of essential amino acids (EAAs) and adequate leucine, are most effective in stimulating MPS. Different types and quality of protein can affect amino acid bioavailability following protein supplementation. Athletes should consider focusing on whole food sources of protein that contain all of the EAAs (i.e., it is the EAAs that are required to stimulate MPS). Endurance athletes should focus on achieving adequate carbohydrate intake to promote optimal performance; the addition of protein may help to offset muscle damage and promote recovery. Pre-sleep casein protein intake (30-40 g) provides increases in overnight MPS and metabolic rate without influencing lipolysis.

A Two-Part Approach to Examine the Effects of Theacrine (TeaCrine®) Supplementation on Oxygen Consumption, Hemodynamic Responses, and Subjective Measures of Cognitive and Psychometric Parameters.

Theacrine (1,3,7,9-tetramethyluric acid) is a naturally occurring purine alkaloid, present in Camellia assamica variety kucha tea. Using a two-part approach in humans, the impact of theacrine (TeaCrine®, TC) was used to examine subjective dose-response, daily changes in cognitive and psychometric parameters, and changes in gas exchange and vital signs. All indicators were chosen to better ascertain the previously reported animal and human outcomes involving theacrine administration. Part 1 was a randomized, open-label, dose-response investigation in nine healthy participants whereby three participants ingested 400 mg TC per day and six participants ingested 200 mg/day. Participants recorded subjective changes in cognitive, psychometric, and exercise attributes using 150-mm anchored visual analog scale (VAS) before, and 1, 4, and 6 hours after ingestion every day for 7 consecutive days. Part 2 was a randomized, double-blind, placebo-controlled, crossover investigation in 15 healthy subjects in which all participants ingested a single 200 mg dose of TC or Placebo (PLA). Anchored VAS questionnaires were used to detect subjective changes in various aspects of physical and mental energy along with changes in gas exchange and hemodynamic parameters before, and 1, 2, and 3 hours after acute ingestion. Energy, focus, and concentration increased from baseline values in both doses with no dose-response effect. VAS responses in the 200 mg for willingness to exercise, anxiety, motivation to train and libido increased across the measurement period while no such change was seen with the 400 mg dose. After consuming a single 200 mg dose, significant group × time interaction effects were seen for energy, fatigue, and concentration. No changes in resting heart rate, gas exchange, systemic hemodynamics or side effect profiles were noted.